The Asp³²⁷Asn Polymorphism in the Sex Hormone-Binding Globulin Gene Modifies the Association of Soy Food and Tea Intake With Endometrial Cancer Risk

Abstract

We evaluated the interactive effect of polymorphisms in the sex hormone-binding globulin (SHBG) gene with soy isoflavones, tea consumption, and dietary fiber on endometrial cancer risk in a population-based, case-control study of 1,199 endometrial cancer patients and 1,212 controls. Genotyping of polymorphisms was performed by using TaqMan (Applied Biosystems, Foster City, CA) assays (rs6259) or the Affymetrix MegAllele Targeted Genotyping System (Affymetrix, Inc., US) (rs13894, rs858521, and rs2955617). Dietary information was obtained using a validated food frequency questionnaire. A logistic regression model was employed to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found that the Asp ³²⁷ Asn (rs6259) polymorphism was associated with decreased risk of endometrial cancer, particularly among postmenopausal women (OR = 0.79, 95% CI = 0.62–1.00). This single nucleotide polymorphism (SNP) modified associations of soy isoflavones and tea consumption but not fiber intake with endometrial cancer, with the inverse association of soy intake and tea consumption being more evident for those with the Asp/Asp genotype of the SHBG gene at Asp ³²⁷ Asn (rs6259), particularly premenopausal women (P _interaction = 0.06 and 0.02, respectively, for soy isoflavones and tea intake). This study suggests that gene–diet interaction may play an important role in the etiology of endometrial cancer risk.

ACKNOWLEDGMENTS

We thank Dr. Fan Jin for her contributions to implementing the study in Shanghai, Drs. Ji-Rong Long and Qing Wang, and Ms. Regina Courtney for their contributions to the genotyping and Ms. Bethanie Hull for her assistance in the preparation of this article. This study would not have been possible without the support of all of the study participants and research staff of the Shanghai Endometrial Cancer Study. This work was supported by United States Public Health Service Grant R01CA92585 from the National Cancer Institute.

Notes

^a Abbreviations are as follows: SHBG, Sex Hormone-Binding Globulin; OR, Odds Ratio; CI, Confidence Interval; Chr, Chromosome. P for 100 times permutation test = 0.45.

^b Hardy–Weinberg Equilibrium.

^c The order of single nucleotide polymorphism rs13894, rs858521, rs6259, and rs2955617 is based on their chromosome position.

^d Not adjusted for any variables.

^a Abbreviations are as follows: SHBG, sex hormone-binding globulin; OR, odds ratio; CI, confidence interval.

^b Age adjusted ORs.

^c The order of SNP rs13894, rs858521, rs6259, and rs2955617 is based on their chromosome position.

^d Unadjusted ORs.

^a Abbreviations are as follows: SHBG, sex hormone-binding globulin; OR, odds ratio; CI, confidence interval. Adjusted for age, education, menopausal status, years of menstruation, number of pregnancies, oral contraceptive use, alcohol consumption, diagnosis of diabetes, body mass index, physical activity, and caloric intake.